Abstract
Bromopropane (BP) compounds, including 1-bromopropane, 2-bromopropane, and 1,2-dibromopropane, are used in industry for various purposes, and their deleterious effects on human health are becoming known. In this study, we examined the effects of BP compounds on the stemness of colorectal cancer cells. At low, non-cytotoxic concentrations, BP compounds significantly increased spheroid formation in CSC221, DLD1, Caco2, and HT29 cells. In addition, the levels of cancer stem cell markers, such as aldehyde dehydrogenase-1, cluster of differentiation 133 (CD133), CD44, Lgr5, Musashi-1, Ephrin receptor, and Bmi-1 increased after exposure to BP compounds. BP compounds increased the transcriptional activity of the TOPflash and glioma-associated oncogene homolog zinc finger protein (Gli) promoters in reporter assays and increased the expression of Gli-1, Gli-2, Smoothened (SMO), and β-catenin by RT-PCR. These results demonstrate for the first time that BP compounds have the potential to promote cancer stemness.
Highlights
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers, and is a major cause of cancer deaths in humans worldwide [1,2]
This study reports the effects of low concentrations of BP compounds on the induction of cancer stemness and the expression of cancer stem cells (CSCs) markers in various CRC cell lines
To determine the cytotoxic range of BP compounds on CRC cells, cell viability assays were performed in various CRC cell lines and in HEK293T cells
Summary
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers, and is a major cause of cancer deaths in humans worldwide [1,2]. Since the risk factors for CRC, such as unhealthy diet, smoking, and obesity, are becoming more common, CRC incidence rates are rapidly increasing in many countries [3]. CRC screening methods and treatments have advanced in recent decades, half of CRC patients experience tumor relapse [4]. The high relapse rate of CRC is thought to be due to the high proportion of cancer stem cells (CSCs), self-renewing cells within tumors [5,6]. CSCs are associated with increased proliferation and invasion and higher rates of tumor relapse and resistance to chemotherapeutics [7,8,9]. The discovery of agents that induce cancer cell stemness is critical for the prevention of CRC
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